Cardiac reflexes conducted by vagal afferents in normotensive and renal hypertensive dogs. 1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals.


Resetting of the baroreceptor in hypotension in rats. 1. A progressive but incomplete adaptation of the aortic baroreceptor was observed after 1 and 6 h of hypotension in rats subjected to controlled bleeding. Administration of phenoxybenzamine produced a greater downward displacement of baroreceptor activation range. 2. Complete adaptation was observed after 48 h of maintained hypotension in rats treated with reserpine. 3. The range of the aortic baroreceptor activation shifted upward as pressure returned to normotension, indicating the reversibility of baroreceptor adaptation in hypotension.


Baroreflex control of coronary conductance in normotensive and renal hypertensive conscious dogs with complete heart block. 1. The autonomic and local control of the circumflex coronary bed evoked through acute rises in aortic pressure (aortic balloon inflation) was analysed in conscious, normotensive and hypertensive dogs in complete heart block with ventricles paced at 100 beats/min. 2. In normotensive dogs there was an initial rise (6-12 s) in circumflex conductance preceding a fall in conductance as aortic pressure increased and was sustained. The initial rise, but not the later fall, in circumflex conductance was partly due to a cholinoreceptor and partly due to alpha-adrenoreceptor mechanisms. Local constrictor mechanisms were responsible for the later fall in conductance. 3. The initial cholinoreceptor component of the rise in circumflex conductance is initiated through arterial baroreflex mechanisms. 4. The initial autonomic mechanisms regulating circumflex conductance appear to be absent in renal hypertension. 5. The absence of the transient autonomic rise in circumflex flow and conductance in response to rapid elevations in aortic pressure in certain forms of hypertension, e.g; during tachyarrhythmias and behavioural disturbances, may result in myocardial ischaemia when it is least appropriate.


Importance of hypertension and genetic factors for atherogenesis in rats. 1. A new experimental system has been used to analyse factors involved in the initiation of atherosclerosis in rats. 2. Arterial fat deposition in the cerebral arteries was affected by blood pressure, serum cholesterol concentrations, strain difference and age, of which high blood pressure was the most important. 3. A genetic factor independent of hypertension was shown to be involved in acute arterial fat deposition in spontaneously hypertensive rats.


Time-course of the reduction of baroreceptor sensitivity in experimental hypertensive rabbits. 1. Hypertension was produced experimentally in three groups of rabbits by atherosclerosis, meical sclerosis and renal encapsulation. 2. The sensitivity of afferent baroreceptor fibre recordings, obtained from an isolated perfused aortic arch preparation, was reduced in all three treated groups. 3. The reduction of baroreceptor sensitivity was directly related to the increase in the lability of the blood pressure in the intact animal and to the reduction of the distensibility of the perfused region. 4. There was a closer relationship between the length of time of rabbits had been hypertensive and the reduction in the baroreceptor sensitivity, than to the level of their blood pressure. 5. The reduction of baroreflex sensitivity obtained by the infusion of phenylephrine was also directly correlated with the period of the hypertension. 6. Baroreceptor resetting occurred to a higher pressure in the renal hypertensive group.


Relationship of age and blood pressure to baroreflex sensitivity and arterial compliance in man. 1. The relationship between baroreflex sensitivity (BRS) and arterial compliance index (ACI) has been investigated (a) in paired subjects matched in one instance for systolic blood pressure with differing ages, and (b) in another instance matched for age with differing systolic blood pressures. 2. There was a significant negative correlation between BRS and age and between ACI and age in the twelve systolic blood pressure-matched subjects. 3. A significant negative correlation of systolic blood pressure with both BRS and ACI was observed in the fourteen age-matched subjects. 4. Both BRS and ACI appear to decrease with increasing age and systolic blood pressure. This decrease in BRS is probably due at least in part to the observed reduction in arterial distensibility.


Effect of intraventricular perfusion of angiotensin II in conscious normal rats and in rats with hereditary hypothalamic diabetes insipidus. 1. Artificial cerebrospinal fluid was perfused through the cerebral ventricles of conscious rats. A basal secretion rate of 16 +/- 3 X 10(-15) mol of immunoreactive angiotensin II/min was calculated for intact rats. 2. Most of the immunoreactive angiotensin II consisted probably of the heptapeptide or pentapeptide angiotensin II fragments. 3. The pressor response to intraventricular perfusions of angiotensin II were normal in Long-Evans rats, virtually absent in rats homozygous for hereditary hypothalamic diabetes insipidus, irrespective of whether they were injected with vasopressin tannate or not, and intermediate in rats heterozygous for hypothalamic diabetes insipidus. 4. The results suggest that the pressor response to intraventricular angiotensin II is related to the release of vasopressin.


Interplay of sino-aortic reflexes and haemodynamic changes during natural sleep in the cat. 1. When the sino-aortic afferents are intact, desynchronized sleep causes a small decrease in the blood pressure, a vasodilation in the mesenteric and renal beds, and a vasoconstriction in the external iliac bed. 2. After sino-aortic deafferentation desynchronized sleep causes a larger fall in the blood pressure, a greater vasodilatation in the mesenteric and renal beds, and a vasodilatation replaces the vasoconstriction in the external iliac bed. 3. The sino-aortic reflexes play an active role in controlling circulation during desynchronized sleep by opposing the centrally induced reduction in adrenergic sympathetic tone. This effect of sino-aortic reflexes is similar on both visceral and muscular vessels. In addition, the muscular bed, but not the visceral one, is regulated by a spinal reflex vasoconstriction mechanism which is apparent only when the sino-aortic reflexes are intact.


Lack of hypotensive effect on central injection of angiotensin inhibitors in spontaneously hypertensive (SH) and normotensive rats. 1. Injections of antagonists of angiotensin II into the cerebral ventricles of normotensive and spontaneously hypertensive rats were performed in order to assess the role of the isorenin-angiotensin system in the brain. 2. No hypotensive effect was obtained in either normotensive or hypertensive rats, suggesting that intracranial isoangiotensin has little role in the pathogenesis of spontaneous hypertension in the rat.


Effect of angiotensin II on noradrenaline content in the rat hypothalamus. 1. Intravenous administration of angiotensin II reduced the adrenaline content, increased the catechol-O-methyltransferase activity, and decreased the monoamine oxidase activity of rat hypothalamus. 2. Intraventricularly administrated angiotensin II reduced the noradreanline content to a smaller extent. 3. The change produced by intravenous administration of angiotensin might be indirectly caused by a response to angiotensin.


Impermeability of the blood-cerebrospinal fluid  barrier for angiotensin II in rats. 1. Anaesthetized, nephrectomized rats were infused intravenously with unlabelled angiotensin II (AII) or with [3H]angiotensin II (3H-labelled AII). The brain ventricular system was perfused with artificial cerebrospinal fluid. The perfusate was collected from the cisterna magna and analysed for AII by radioimmunological and biochemical methods. 2. No increase of immunoreactive AII in cerebrospinal fluid could be shown during intravenous infusion of AII. 3. During intravenous infusions of 3H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate. 4. The radioactivity of cerebrospinal fluid outflow could not be related to AII.


Blood pressure response to central and peripheral injection of angiotensin II and 8-C-phenylglycine analogue of angiotensin II in rats with experimental hypertension. 1. We have compared the effect of central and peripheral administration of angiotensin II and (1-succinamoly-5-valine-8-phenylglycine)angiotensin II on blood pressure of male conscious unrestrained rats with normal blood pressure, and with spontaneous hypertension or chronic renal hypertension. 2. After central and peripheral injection of angiotensin II all rats exhibited a significant dose-related increase in blood pressure. 3. Administration of the analogue was without effect in normotensive rats. Ten-weeks-old rats with spontaneous hypertension showed a significant blood pressure decrease after central injection, but an increase after peripheral injection. This centrally induced decrease could not be observed in spontaneously hypertensive rats 14 weeks old. In these animals the analogue increased the blood pressure. In rats with chronic renal hypertension in contrast to peripheral injection, central administration decreased the pressure significantly. 4. Plasma renin activity was not changed after central injection of the analogue in normotensive rats. 5. These observations suggest the participation of the intrinsic brain isorenin-angiotensin system in central blood pressure regulation in these forms of experimental hypertension.


Some factors influencing the damaging effect of acute arterial hypertension on cerebral vessels in rats. 1. Abrupt increase of arterial blood pressure can give rise to multifocal areas of protein extravasation in the brain due to overstretching of the vessels. 2. The vascular tone of the resistance vessels is of importance for the occurrence of the increased permeability. 3. Vasodilatation aggravates the damaging effect of acute hypertension whereas vasoconstriction induced by hyperventilation reduces the incidence of areas of increased permeability. 4. Ligation of a carotid artery prevents lesions in the ipsilateral hemisphere.


Reduction of the hypotensive effect of clonidine and alpha-methyldopa by various psychotropic drugs. 1. In chloralose-anaesthetized cats the centrally induced hypotensive effect of clonidine, and in some cases alpha-methyldopa, was diminished by pretreatment with a variety of tricyclic antidepressants and neuroleptic agents. 2. The interaction is assumed to occur at the central alpha-adrenoreceptors. Clonidine or alpha-methyl-noradrenaline (from alpha-methyldopa) are the agonists, and the aforementioned psychotropic drugs are the antagonists. 3. Psychotropic drugs which are not alpha-receptor blockers, like butyrophenone neuroleptics (pimozide and haloperidol) or benzodiazepine tranquillizers, do not significantly diminsh the centrally induced hypotensive effect of clonidine.


Enhancement of the anti-hypertensive effect of methyldopa and other anti-hypertensive drugs by carbidopa in spontaneously hypertensive rats. 1. A peripheral inhibitor of L-aromatic amino acid decarboxylase, carbidopa [(-)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate], at doses up to 25 mg/kg intraperitoneally or 30 mg/kg orally had no effect on directly recorded arterial pressure of spontaneously hypertensive rats derived from the Wistar/Okamoto strain. It enhanced, however, the anti-hypertensive effects of methydopa, hydrallazine, guanethidine and clonidine, and, to a lesser extent, reserpine and hydrochlorothiazide. The mechanism of this enhancement is presently unkonwn, but biochemical studies support the assumption that carbidopa is likely to reduce sympathetic nervous system activity. 2. The conversion of [3H]tyrosine (given intraperitoneally) to dopa (3,4-dihydroxypheylalanine) and catecholamines was measured in the hearts and adrenals of control rats and animals pretreated with carbidopa (100 mg/kg, intraperitoneally). Carbidopa significantly decreased the accumulation of 3H-labelled catecholamines in both organs and increased their total tyrosine content and the specific radioactivity of tyrosine.


Neural and non-neural mechanisms in spontaneous hypertension. 1. The pathogenesis of hypertension in spontaneously hypertensive rats (SHR) is considered to consist of neurogenic and non-neurogenic factors, both of which contribute to initiation and maintenance mechanisms. 2. Neurogenic factors have been demonstrated by the destruction of the central nervous system, sympathectomy, recording of sympathetic discharge, hind-limb perfusion and study of noradrenaline. These factors are mainly involved in the initiation of hypertension, and they appear to diminish in importance after the establishment of hypertension, as indicated by the noradrenaline-turnover study. 3. The non-neurogenic factors have been demonstrated haemodynamically by increased peripheral vascular resistance remaining even after sympathectomy. They have also been demonstrated histologically by the narrowing of resistance arteries with medial hyperplasia or hypertrophy. These factors appear to participate in maintenance mechanisms. 4. Increased incorporation of labelled amino acid into non-collagenous and collagenous protein of the arterial walls precedes medial hypertrophy and hyertensive arteriosclerosis. It seems to play a role therefore both during neurogenic initiation and later non-neurogenic maintenance of blood pressure. 5. Non-collagenous protein metabolism of arterial walls is increased in young SHR, and it is partly dependent on neural innervation as detected by surgical or pharmacological sympathectomy. It indicates a close linkage between neurological and structural changes in the initiation of spontaneous hypertension.


Sympathotonia in primary hypertension and in a caricature resembling dysautonomia. 1. Plasma catecholamines and adrenergic correlates of cardiac function were compared in young men with borderline hypetension, classified according to renin status (group 1). Plasma catecholamines were increased and cardiac pre-ejection periods were shortened in 'high'-renin patients. 2. Plasma catecholamines were raised in 70% of 'high'-renin patients with primary hypertension (group 2), were related directly with age in normotensive females and were related inversely with catecholamine responses to postural stress in both normotensive and hypertensive subject (P less than 0-01). 3. The raised catecholamines of four 'high'-renin patients with pronounced features of sympathetic nerve activity-acricatures were elevated further during,hypertensive periods. Mean arterial blood pressures were reduced 20-30% after either alpha- or beta-receptor blockade. Catecholamines were reduced after beta-receptor blockade. 4. There appears to be a spectrum of neurogenic 'gain' in primary hypertension; it is suppressed in 'low'-renin hypertension, directly related to blood pressure in 'normal'-renin hypertension, increased in 'high'-renin hypertension and achieves a maximum in caricatures. Neurogenic factors seem to be important in the cause and maintenance of 'high'- and 'normal'-renin hypertension respectively. The caricatures may be examples of a severe form of hypothalamic stimulation.


Plasma noradrenaline and renovascular hypertension in the rat. 1. Plasma noradrenaline was measured in groups of rats up to 4 weeks after application of a renal artery clip. 2. When renal artery clipping was accoumpanied by contralateral nephrectomy (one-kidney model) plasma noradrenaline was significantly higher in hypertensive rats than in sham-operated control rats at 7, 14 and 28 days. 3. Plasma noradrenaline was not altered at any time examined in the two-kidney model (unilateral clip and contralateral kidney left in situ). 4. Neurogenic mechanisms mediated by the peripheral sympathetic nervous system appear to participate in the development of one-kidney renovascular hypertension, but do not play a significant role in the two-kidney model.


Anti-hypertensive effect of metoprolol in spontaneously hypertensive rats. 1. Oral and intravenous administration of metoprolol to adult spontaneously hypertensive rats (SHR) with established hypertension lowered arterial blood pressure within 4 days of treatment. 2. Steady state plasma concentrations of metoprolol were similar to those of patients during anti-hypertensive treatment with this drug. 3. The neuroeffector function of portal veins of SHR treated orally for 14 days or intravenously for 4 days was not impaired when studied in vitro. This is in contrast to previous findings after long-term treatment. 4. It is concluded that the anti-hypertensive effect of metoprolol in SHR in many respects resembles that observed in patients. It is suggested that impairment of vasomotor nerve control may contribute to the anti-hypertensive effect of beta-adrenoreceptor antagonists.


The effects of propranolol on spontaneous and experimental hypertension in the rat. 1. The hypotensive effect of propranolol and its correlation with the changes in heart rate, plasma volume and plasma renin activity produced by this drug were studied in normotensive rats and in rats with spontaneous, renovascular and deoxycorticosterone-induced hypertension. 2. No correlation was found between the fall in arterial pressure and the reduction in heart rate and plasma volume. On the contrary, a direct correlation was found between the hypotensive response and plasma renin activity: rats with high renin showed the maximum response, those with low renin no response. 3. Studies on blood volume distribution in different organs and the direct measurement of blood flow in the splanchnic bed demonstrated a significant correlation between the effect of propranolol on capillary permeability and the haemodynamic changes which it causes, namely a significant increase in portal venous pressure.


Vasopressin and malignant deoxycorticosterone hypertension in rats. 1. The role of arginine-vasopressin in the pathogenesis of malignant deoxycorticosterone (DOC) hypertension of rats was investigated. 2. In rats with malignant DOC hypertension plasma arginine-vasopressin concentrations increased more than tenfold subsequent to volume depletion and a rise of serum osmolality. 3. The injection of a specific antibody serum for arginine-vasopressin caused a marked fall of blood pressure in rats with malignant DOC hypertension, whereas the injection of angiotensin II antiserum did not affect blood pressure. 4. In rats exhibiting a benign course of DOC hypertension plasma concentrations of arginine-vasopressin were increased threefold in comparison with normotensive control rats; the injection of an arginine-vasopressin antiserum induced a significant but small fall of blood pressure. 5. It is concluded that in the pathogenesis of malignant DOC hypertension arginine-vasopressin might play the role that the renin-angiotensin system plays in the pathogenesis of malignant renal hypertension.


Interaction of angiotensin II with catecholamines in the circulation of the dog and cat. 1. The blood-bathed organ technique was employed to study the effects of angiotensin II and catecholamines on an isolated everted rat aorta bathed in the extracorporeal circulating blood of adult dogs and cats. 2. When the injections were made into the bathing blood close to the everted rat aorta, angiotensin II was half as potent as adrenaline or noradrenaline on a molar basis. 3. After intravenous injections, the vasoconstrictor potency of angiotensin was twenty times that of adrenaline or noradrenaline on the everted rat aorta. The increase in potency was due to the interaction of angiotensin II with catecholamines on the preparation. 4. Intravenous phenoxybenzamine abolished the potentiated vasoconstrictor effect of angiotensin II on the blood-bathed everted rat aorta, but it did not abolish the pressor effect of angiotensin II on the cardiovascular system of the animals. The results suggest that catecholamines released into the circulating blood by intravenous angiotensin II do not play an important role in the pressor effect of angiotensin II.


Anti-hypertensive effect of acebutolol: its relation to sympathetic nervous system responsiveness and to plasma renin and dopamine-beta-hydroxylase activities. 1. Acebutolol, a beta1-receptor blocker, has, at a daily dose of 800 mg, a mild but significant anti-hypertensive effect in moderate sustained essential hypertension with normal or low plasma renin activity. 2. Prediction of its anti-hypertensive effect is better based on the evaluation of the sympathetic nervous system responsiveness to head-up tilt than on the evaluation of plasma renin activity or dopamine-beta-hydroxylase. 3. The anti-hypertensive effect of acebutolol is better explained on the basis of inhibition of the sympathetic nervous system activity than on the basis of suppression of plasma renin activity. 4. A positive correlation between plasma renin activity and dopamine-beta-hydroxylase in patients on diuretics suggests the common dependence of these two variables on sympathetic overactivity.


Serum dopamine beta-hydroxylase activity in essential hypertension. 1. Serum dopamine beta-hydroxylase activity was determined in normotensive control subjects and patients with labile or established essential hypertension. The enzyme activity was 25-9 +/- 1-9 (SEM) 29-6 +/- 2-5 and 25-1 +/- 1-9 micronmol min-1 1-1, for control, labile and established hypertensive subjects respectively. 2. Neither blood pressure nor serum dopamine beta-hydroxylase activity was changed in normotensive control subjects by administration of phentolamine; however, in patients with essential hypertension blood pressure was significantly decreased (P is less than 0-01) and serum dopamine beta-hydroxylase activity was slightly increased. With propranolol administration, blood pressure and the serum enzyme activity were not significantly changed in normotensive or hypertensive subjects. 3. Our results suggest that there is no correlation between serum dopamine beta-hydroxylase activity and blood pressure.


Effect of long-term anti-hypertensive beta-receptor-blocking treatment on haemodynamic and metabolic responses to prolonged exercise in man. 1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective beta-receptor-blocking drug (alprenolol). 2. Alprenolol treatment (200-400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise. 3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.


Vascular lesions in hypertensive rats under salt loading: kidney renin and lysosomal enzymes. 1. Renal and cerebral vascular lesions occurred more often and earlier in spontaneously hypertensive rats (SHR) given a high salt diet than in SHR given a normal diet. 2. Kidney renin activity was low during high salt loading; the kidney renin activity of rats with hypertensive renal vascular lesions was moderately elevated. Kidney renin activity or cathepsin D activities were higher in stroke-prone SHR (SHRSP) aged 9 months than in stroke-resistant SHR (SHRSR). 3. beta-Glucuronidase, cathepsin D and deoxyribonuclease activities were greater in the kidney of Wistar/Kyoto (WK) rats or SHR when there were hypertensive vascular lesions. These three enzyme activities were also greater in the aorta of SHR aged 13-14 months than in the aorta of WK rats. 4. It was supposed that kidney renin activity and lysosomal enzyme activities were related to hypertensive vascular lesions.


Increased plasma noradrenaline concentrations in essential hypertension and their decrease after long-term treatment with a beta-receptor-blocking agent (prindolol). 1. Plasma noradrenaline was measured in fifty-nine patients with mild to severe essential hypertension and in fifteen normotensive control subjects under basal and orthostatic conditions. 2. In patients with essential hypertension mean plasma noradrenaline concentrations were significantly higher than in control subjects under basal and orthostatic conditions. 3. In patients with essential hypertension basal diastolic blood pressure correlated closely with the corresponding plasma noradrenaline concentrations. 4. Long-term treatment with prindolol of patients with essential hypertension led to a significant fall in diastolic and systolic blood pressure and heart rate and to a significant decrease in plasma noradrenaline concentrations under basal and orthostatic conditions. 5. The adrenergic response to upright posture, reflected by an increase in plasma noradrenaline, was not abolished by prindolol. 6. It is concluded that the anti-hypertensive effect of prindolol in patients with essential hypertension is at least partially mediated by a decrease of sympathetic nervous activity.


Haemodynamic responses to exercise and acute beta-receptor blockade in renin sub-types of essential hypertension. 1. Haemodynamic and renin responses to dynamic exercise before and after intravenous beta-adrenoreceptor blockade with propranolol were compared in twenty-one patients with essential hypertension and either high (n = 7), normal (n = 7) or low plasma renin activity (n = 7). 2. Renin and heart-rate responses to exercise and beta-receptor blockade diminished from high-renin to normal and to low-renin patients, effects which were blunted with increasing age. 3. Among the renin groups cardiac output, stroke volume, diastolic pulmonary artery pressure, systemic pressure and peripheral vascular resistance as well as their changes produced by exercise and acute beta-receptor blockade were not significantly different. 4. Long-term anti-hypertensive propranolol effects correlated with pre-treatment renin status, renin stimulation and its suppression by acute beta-receptor blockade as well as with the exercise tachycardia and the patient's age. 5. The results suggest different adrenergic control mechanisms in renin sub-types of essential hypertension, age being a modulating factor.


Combined alpha- and beta-adrenoreceptor blockade in hypertension: a controlled trial of labetalol (AH 5158) compared with propranolol and placebo. 1. Labetalol (AH 5158) is a new drug which has both alpha- and beta-adrenoreceptor antagonist activity. Labetalol has been compared with propranolol and placebo for the treatment of mild to moderate hypertension (150/100 to 189/114 mmHg), in a double-blind cross-over trial with three 10 week treatment periods. 2. Both drugs reduced blood pressures in nine of the ten patients who have completed the trial. Relative to placebo labetalol caused decreases in supine pressures similar to those caused by propranolol (average -10/-10 and -10/-9 mmHg respectively), with a greater effect on standing (labetalol -20/-19; propranolol -8/-12 mmHg; P less than 0-01) and after exercise (labetolol -27/-18 and propranolol -16/-14 mmHg). 3. Labetalol and propranolol caused a similar fall in supine pulse rate (-11/min and -13/min respectively), but there was less bradycardia on standing (labetalol -11/min; propranolol -18/min; P less than 0-001) and after exercise (labetalol -17/min; propranolol -23/min; P less than 0-001). 4. The average dose ratios of labetalol to propranolol was 2-4:1 (w/w). 5. These results suggest that the effect of labetalol on blood pressure involves both alpha- and beta-adrenoreceptor antagonist properties. 6. Further evaluation of labetalol is warranted as it may have some advantages in respect of producing less bradycardia, improved peripheral blood flow and less effect on airways resistance than 'pure' beta-receptor-blocking agents.


Effects of intravenous labetalol on blood pressure, angiotensin II and aldosterone in hypertension: comparison with propranolol. 1. Labetalol, a compound with both alpha- and beta-adrenoreceptor-blocking actions, was given intravenously (1-5-2-0 mg/kg) in twenty recumbent hypertensive patients. 2. There was a rapid reduction in systolic and diastolic pressures in all, maintained up to 24 h in some subjects. 3. Severe hypotension was not seen in recumbent subjects, but postural hypotension was common. 4. Labetalol caused significant lowering of heart rate. 5. Labetalol induced significant and related lowering of plasma angiotensin II and aldosterone concentrations, most obviously when these were initially high. 6. In a cross-over comparison in five patients against 10 mg of propranolol intravenously, labetalol was more effective in lowering blood pressure, but less effective in lowering pulse rate or plasma angiotensin II.


The effect on blood pressure of beta-adrenoreceptor-blocking drugs given once daily. 1. Blood pressure was controlled to the same extent whether propranolol or pindolol was given once or three times/day. 2. The anti-hypertensive action of beta-receptor-blocking drugs persisted for 36-48 h when administration ceased.


Effects of noradrenaline on consecutive vascular segments at low or normal calcium concentrations in control and spontaneously hypertensive rats. 1. An 'isogravimetric' technique, plus measurement of pressure in a small artery, was used to investigate the responses of upstream and downstream precapillary and postcapillary resistance vessels in the hindquarters of spontaneously hypertensive rats (SHR) and normal control rats perfused at constant flow. 2. Dose-response curves to noradrenaline were constructed under conditions of low or normal calcium. 3. In both control rats and SHR the dependence on external calcium during contraction increased peripherally, with the smaller pre- and post-capillary resistance vessels being most dependent and larger arteries least dependent. 4. There may be differences between SHR and control rats in regard to the handling of calcium, particularly in the small pre- and post-capillary resistance vessels.


Compared incidence of first myocardial infarction in hypertensive patients under treatment containing propranolol or excluding beta-receptor blockade. 1. After some exclusions, 169 severe uncomplicated essential hypertensive patients presenting consecutively were divided into two groups according to their treatment. Of these, 121 had been given longterm treatment containing propranolol (PC group) and forty-eight had been treated with hypotensive agents excluding any beta-receptor-blocker group, the non-beta-receptor-blocker (NBB) group. 2. There were no significant differences in myocardial infarction risk factors between the two groups. 3. After a mean follow-up of 5-25 years, nine of the 121 subjects (7-5%) in the PC group had suffered first infarctions and fifteen of the forty-eight subjects (31%) in the NBB group, a significant difference (P less than 0-01). 4. It was concluded that the presence of propranolol had prevented more or caused fewer infarctions, perhaps a combination of both, than had the older hypotensive agents unsupported by beta-receptor blockade.


Clinical trial of the beta-adrenoreceptor-blocking agent tolamolol with the use of 24 hour blood pressure recordings. 1. The average blood pressure over 24 h and its variability were measured in eight unrestricted subjects before and after commencing therapy with a new beta-adrenoreceptor-blocking agent, tolamolol. 2. The drug caused a fall of 15 +/- 6 mgHg in mean arterial pressure and heart rate fell by 13 beats/min. The variation in blood pressure and heart rate over 24 h was unchanged after treatment.


beta-receptor-blockade hypotension and the central nervous system. 1. Intravenous infusion of propranolol (3-86 micronmol h-1 kg-1) for 2 h lowered arterial pressure in the conscious rabbit whereas similar infusions of practolol (37-6 micronmol h-1 kg-1) did not. 2. The fall in blood pressure produced by propranolol was accompanied by a decrease in splanchnic nerve activity. Practolol did not change splanchnic nerve activity. 3. A centrally mediated decrease in sympathetic nervous activity makes an important contribution to the hypotensive action of propranolol in the rabbit. This effect is not shown by practolol.


Comparison of metoprolol and propranolol in modification of haemodynamic and renin-aldosterone responses to tilting in humans. 1. Acute oral administration of metoprolol and propranolol to ten normal males resulted in equal reduction in heart rate both supine and after passive tilting to 60 degrees. 2. Tilted systolic blood pressure was reduced by both agents but metoprolol alone reduced supine systolic blood pressure. 3. Tilted but not supine diastolic blood pressure was reduced by both agents. 4. Metoprolol and propranolol both reduced the rise in plasma renin activity induced by tilting. 5. No effect of tilting was observed on plasma aldosterone.


Increase of total body potassium and decrease of exchangeable sodium after long-term treatment with a beta-receptor-blocking agent (prindolol) in essential hypertension. 1. The effect of long-term treatment with prindolol on blood pressure, total body potassium (Kt), exchangeable sodium (Nae) and plasma renin activity was investigated in twelve patients with essential hypertension. 2. Systolic and diastolic pressures were significantly reduced from 164/112 to 127/90 mmHg under basal conditions. 3. Before treatment Nae in patients with essential hypertension was significantly higher than in normotensive individuals. After an average of 16 weeks on prindolol Nae in patients with essential hypertension was significantly decreased, despite an average increased in body weight of 2 kg in the patients. 4. In contrast to the decrease in Nae, Kt was found to be significantly increased after long-term treatment with prindolol. Kt values of patients before and after prindolol, however, did not differ significantly from the corresponding sex- and age-dependent normal values. 5. Plasma renin activity was slightly diminished under basal and orthostatic conditions; the stimulatory effect orthostatis was not abolished but reduced by prindolol. 6. It is suggested that the changes in sodium balance contribute to the anti-hypertensive effect of prindolol in patients with essential hypertension.


Comparison of a slow-release formulation of oxprenolol with conventional oxprenolol in the treatment of hypertension. 1. Patients with moderate to severe hypertension were studied during a 12 weeks period, while taking a slow-release formulation of oxprenolol once daily, in a dose equal to their previous total daily dose of oxprenolol given in divided doses. 2. There were no significant differences between blood pressure at the beginning and end of the 12 weeks period. 3. Once-daily dosage offers advantages of patient compliance.


The use of minoxidil in the treatment of severe essential hypertension: a report on 100 patients. 1. One hundred patients with severe essential hypertension have been treated with minoxidil for a mean period of 8-4 months in a study involving eleven European centres. Seventy-two males and twenty-eight females were included in the group; the mean age was 55 years and the initial supine systolic and diastolic pressures averaged 212 (range 150-270) and 125 (range 90-150) mmHg respectively. 2. Reduction of supine diastolic pressure to less than 100 mmHg occurred in 94% of patients within 4 weeks. After the average follow-up period of 8-4 months the mean pressures were 151/91 mmHg. Concomitant therapy with beta-receptor-blocking agents and diuretics resulted in satisfactory control of heart rate and weight gain. 3. Side effects included increased hair growth, nausea, fatigue, rash and darkening of the skin. ECG showed mainly T-wave changes and echocardiographic examination indicated improved ventricular emptying.


Cardiac function in the treatment of arterial hypertension with propranolol. 1. Propranolol, when used for treating arterial hypertension, may influence determinants of both cardiac and vascular function; the consequent changes in cardiac performance may result from the interaction of different and possibly opposite effects. 2. Cardiac funtion was investigated in fifty-four primary hypertensive men in the pretreatment state and after 3 weeks of propranolol therapy at a daily dose of 320 mg. 3. beta-Receptor blockade caused depression of pre-injection left ventricular function, which was unrelated to the direction and the extent of changes in peripheral circulation. 4. The ejection left ventricular function could be either depressed or improved depending on the direction to which treatment shifted the vascular resistance, and consequently, the impedance to left ventricular ejection. 5. Withdrawal of the adrenergic support is probably the major factor responsible for the poor ventricular adaptation to an augmented impedance.


Vasodilating drugs: contrasting haemodynamic effects. 1. We investigated the haemodynamic effects of intravenously administered hydrallazine, diazoxide and nitroprusside and orally administered minoxidil to determine whether vasodilators (such as nitroprusside) which do not increase cardiac output might be better treatment for hypertensive complications associated with, or caused by, myocardial failure than those that do. 2. Hydrallazine and diazoxide caused increases in heart rate, cardiac output, cardiopulmonary blood volume, the ratio of cardiac output to cardiopulmonary volume, and pulmonary artery pressure. Nitroprusside, although decreasing pressure and vascular resistance, caused no significant change in the other functions except for reducing pulmonary artery pressure. Minoxidil, when given orally, had the potential for causing pulmonary hypertension. This seemed explained by increased flow (hyperdynamic type) in some but by congestive cardiac failure in others; the latter condition was probably intensified by the marked fluid retention that the drug can cause. 3. On the basis of these results a classification of vasodilators was constructed which depends on the presence or absence of a venodilating effect. Vasodilators which produce no (or little) venodilatation, increase heart rate, cardiac output, cardiopulmonary blood volume and pulmonary artery pressure. In this class are diazoxide, hydrallazine and minoxidil. Those that cause venodilatation do not stimulate the heart nor do they cause pulmonary hypertension. Nitroprusside and nitroglycerine are drugs of this type. 4. These results suggest that drugs producing both venodilatation and arteriolar dilatation may be more specific therapy for hypertensive complications associated with cardiac failure than those that cause only arteriolar dilatation.


Clinical and haemodynamic study of minoxidil in moderately hypertensive patients. 1. We have evaluated the effectiveness and safety of minoxidil in moderately hypertensive out-patients. Eight patients were treated with hydrochlorothiazide and minoxidil for 5 months. The only female patient developed slight, reversible facial hair growth. In the other seven patients there was a moderate decrease in blood pressure. There were only minimal side-effects. Mild exertional tachycardia and a mean increase in body weight of 0-5 kg was found, but no oedema or signs of cardiac insufficiency were observed. No abnormalities were seen during routine blood tests. 2. This study shows that minoxidil combined with a diuretic may be successfully used in treating moderately hypertensive male patients.


Assessment of autonomic and non-autonomic components of resting hindlimb vascular resistance and reactivity to pressor substances in renal hypertensive rabbits. 1. Hindlimb vascular resistance (HVR) was measured before and after pharmacological autonomic blockade in unanesthetized renal cellophan-wrap hypertensive or normotensive rabbits with previously implanted Doppler ultrasonic flowmeters. 2. When the blood pressure was restored to resting values after autonomic block, the elevated resting HVR in the hypertensive rabbits was entirely accounted for by an increased non-autonomic component (i.e. HVR after block). If the pressure was not restored after block the autonomic component (i.e. resting HVR minus non-autonomic HVR) was overestimated and the non-autonomic component was underestimated. 3. During maximum vasodilatation the minimum HVR was significantly higher in the hypertensive rabbits than in the normotensive group, probably due to structural differences of resistance vessels. 4. Reactivity of the hindlimb bed to noradrenaline, angiotensin II and vasopressin injections was approximately twice as great in the hypertensive rabbits as in the sham-operated group, probably as a consequence of the structural changes.


Haemodynamic and endocrinological changes during anti-hypertensive treatment with a new vasodilator substance (L6150) and propranolol. 1. In eighteen subjects with mild to moderate hypertension the effectiveness of the new vasodilator drug L6150 (Lepetit) was studied. Its mechanism of action was identified by systemic and renal blood flow measurements and by estimating changes in plasma renin and aldosterone concentration and plasma volume. The reflexly induced hyperkinetic circulatory state could be completely corrected by adding propranolol or prevented by pretreatment with the latter drug. 2. Sodium retention was an invariable phenomenon. It was not due to a stimulation of the reninangiotensin-aldosterone axis since plasma aldosterone was significantly decreased, presumably as a consequence of plasma volume expansion.


Treatment of severe hypertension with minoxidil and its effects on systemic and pulmonary haemodynamics. 1. The chronic administration of minoxidil, 0-024-0-212 mmol (5-40 mg) daily, to fifty-two severely hypertensive patients resulted in an average reduction of mean arterial pressure from 170 to 111 mmHg. 2. Haemodynamic studies in twelve of these patients indicated that the rise in pulmonary arterial pressure in patients without heart failure appears to be a direct result of a disproportionately large increase in cardiac output with respect to a relatively small decrease in pulmonary vascular resistance. Anti-hypertensive treatment of patients with congestive heart failure resulted in a decrease in mean pulmonary arterial pressure.


Treatment of hypertension in middle-aged men: a feasibility study in a community. 1. In a health examination survey of 2322 men, aged 49-50 years, the prevalence of hypertension was 7-5%. All men with a supine diastolic blood pressure greater than or equal to 105 mmHg were invited to a hypertension clinic. 2. Two years' treatment in eighty-six men achieved a blood pressure reduction of 31/16 mmHg, which was maintained for a 4 years period and considered satisfactory in 80% of the subjects. Propranolol was used in more than 80% of the cases. 3. The study indicates that it is possible to obtain acceptable blood pressure control in the community.


Cardiovascular effects of prazosin in dogs. 1. In pentobarbitone-anaesthetized dogs, prazosin (2 x 1-3 micronmol day-1 kg-1; 2 x 0-5 mg day-1 kg-1) administered orally for 3 days reduced resting aortic blood pressure as well as the pressor response to bilateral carotid occlusion. Prazosin neither affected resting heart rate nor the tachycardia induced by intravenous isoprenaline, noradrenaline and electrical stimulation of preganglionic and postganglionic sympathetic nerve fibres. Prazosin significantly attenuated the fall in perfusion pressure in a perfused hind leg resulting from the section of the ipsilateral sympathetic lumbar chain. Furthermore, the drug inhibited by about 50% the hind-leg pressor responses elicited by intra-arterial administration of alpha-adrenoreceptor agonists and by stimulation of the lumbar sympathetic chain, without altering the effects of angiotension II. 2. Acute administration of prazosin into the innervated hind leg provoked a dose-related reduction in vascular resistance. However, after spinal anaesthesia no such an effect was observed even when vascular tone was increased by infusion of vasopressin. Under the same experimental conditions administration of papaverine induced a vasodilatation. 3. This study confirms that prazosin impairs the function of vascular alpha-adrenoreceptors, and strongly challenges the claim that this compound produces a directly mediated vasodilatation of the leg vascular bed.


A study of the use of prazosin in hypertensive patients in Korea. 1. The effects of prazosin administered alone or in combination were studied in thirty patients between August 1974 and March 1975. 2. All patients had previously received treatment for hypertension with other agents, for from 2 months to 10 years. All thirty patients had refractory hypertension which had not responded satisfactorily to other treatment. 3. Patients were treated initially with prazosin; polythiazide, or polythiazide plus tolamolol, were added when necessary. 4. A satisfactory blood pressure response to prazosin alone, or prazosin in dual or triple combination therapy, occurred in all thirty patients. 5. Prazosin was well tolerated.


Changes in vascular smooth muscle sensitivity to vasoconstrictor agents induced by corticosteroids, adrenalectomy and differing salt intake in rats. 1. Isolated hind limbs of rats were perfused and vascular smooth muscle sensitivity to noradrenaline, methoxamine and potassium chloride was measured and dose-response curves were obtained. 2. The sensitivity of vascular smooth muscle to noradrenaline is attenuated by adrenalectomy and low sodium diet; it is enhanced by corticosterone. High sodium diet or administration of deoxycorticosterone did not alter the dose-response curve significantly. 3. The increased sensitivity of vascular smooth muscle after corticosterone treatment is not related to changes in the contractile protein or alterations in the neuronal uptake and extraneuronal metabolism of noradrenaline. 4. These results suggest that the increased sensitivity in corticosterone-treated rats may be due to the number of receptors, receptor affinity to noradrenaline, or changes in the functional link between receptor and contractile apparatus.


Prazosin and hydrallazine in the treatment of hypertension. 1. Two vasodilators, prazosin and hydrallazine, have been compared in three double-blind cross-over studies designed to test their effect when used in combination with a beta-adrenoceptor-blocking agent and a thiazide. 2. Single doses of 3 mg of prazosin or 75 mg of hydrallazine were administered to patients whose blood pressures remained uncontrolled on a thiazide and a beta-adrenoceptor-blocking agent. Both agents produced significant falls in systolic and diastolic blood pressure apparent at 1 h. The effects of prazosin persisted for 6-7 h and those of hydrallazine for 4-6 h. Tachycardia was more marked and more prolonged after hydrallazine and continued after the blood pressure had risen to base-line levels or above. 3. In 6 week and 12 week double-blind cross-over studies, mean falls in blood pressure were similar with prazosin and hydrallazine. Similar falls in the supine diastolic blood pressure were achieved with 1 mg of prazosin and 20 mg of hyrallazine, but for a given fall in supine diastolic blood pressure, prazosin produced a significantly lower standing diastolic blood pressure. 4. Severe side effects were more pronounced after hydrallazine, which necessitated withdrawal of seven patients, whereas only one patient on prazosin withdrew from the trial because of side effects.


A comparison of the effects of chlorothiazide and of metolazone in the treatment of hypertension. 1. A cross-over study was done in twenty patients with hypertension to compare the effects of chlorothiazide (0-5 g twice daily) and metolazone (5 mg daily) in combination with other anti-hypertensive agents. 2. Compared with absence of diuretic therapy, chlorothiazide and metolazone both produced significantly lower blood pressures. 3. Blood pressures on metolazone tended to be lower than on chlorothiazide but this difference was not statistically significant. 4. Both diuretics significantly lowered serum potassium concentrations and total body potassium to a similar degree, but the serum potassium did not fall below the normal range in any patient and no potassium supplements were needed. No electrocardiographic changes suggestive of hypokalaemia were noted. 5. Small but significant increases in serum bicarbonate, calcium, urea and acid were observed with both diuretics. 6. Patient acceptance was excellent and no adverse effects were encountered.


Relative effectiveness of chlorothiazide, reserpine and hydrallazine in spontaneously hypertensive rats. 1. Previous studies in this laboratory indicated that a mixture of anti-hypertensive agents in the drinking water controlled the blood pressure of spontaneously hypertensive rats (SHR). The present study was designed to determine which of the agents exerted the greatest anti-hypertensive effect. 2. Treatment was begun at 12 weeks of age in groups of eleven to seventeen rats with one of the following drugs: reserpine, chlorothiazide or hydrallazine. Blood pressures were recorded by the tail method under light ether anaesthesia every 2 weeks until the rats were approximately 70 weeks of age. 3. At 50 weeks of age, blood pressure of chlorothiazaide-treated rats averaged 40 mmHg below untreated control SHR; reserpine-treated SHR were also 40 mmHg lower than control rats, and hydrallazine-treated SHR were 85 mmHg below the control rats. 4. Rats in all groups gained weight normally and appeared in good health. Although all drugs were active, hydrallazine was considerably more effective than chlorothiazide or reserpine in the SHR.


Pharmacokinetic and pharmacological studies with clonidine in normal subjects. 1. A highly specific and sensitive assay based on stable isotope dilution and mass fragmentography has been developed to measure clonidine in plasma. 2. Plasma half-lives of clonidine ranged from 6-9 to 9-4 h in five normotensive subjects. 3. Plasma clonidine concentration correlated with reduction in salivary flow and degree of sedation but not with change in blood pressure.


Comparison of the effects of pharmacological therapy and a low-sodium diet on mild hypertension. 1. The effect of a low-sodium diet and pharmacological therapy has been compared in eighty-one patients with mild hypertension. 2. Both pharmacological therapy and a low-sodium diet reduced lying and standing systolic and diastolic blood pressure significantly.


Haemodynamic and endocrine changes during anti-hypertensive treatment with clonidine and its derivative St 600. 1. The cardio-renal haemodynamic and endocrine effects of the anti-hypertensive agents 2-(2,6-dichlorophenylamine)-2-imidazoline hydrochloride (clonidine, St 155) and 2-(5-fluor-o-toluidine)-2-imidazoline hydrochloride (St 600) were investigated in twelve patients with essential hypertension. 2. The anti-hypertensive action of both compounds was similar and was accompanied by a reduction in heart rate and in cardiac output, total peripheral resistance being unchanged. There was no alteration in renal blood flow and glomerular filtration rate, and renal vascular resistance showed a significant decrease. Blood volume and plasma renin concentration did not change significantly. An inverse relation changes in plasma volume and plasma aldosterone concentration was observed. In the face of similar reductions in blood pressure, no differences were observed between systemic and renal haemodynamic and endocrine responses after clonidine and St 600.


Characteristics and prognosis for women with hypertension in a community: results of a longitudinal study in Göteborg, Sweden. 1. During the years 1968-69 a population study of 1462 women aged 38-60 years was carried out in Göteborg, Sweden. A total of 126 women were classified as hypertensive. 2. Hypertensive women reported a history of albuminuria and hypertension during pregnancy more often than women in the general population. Albuminuria, alterations of the eye-ground vessels and ECG changes indicating left ventricular strain were more often found in hypertensive women. Hypertensive women were on average heavier. 3. The same population sample was re-studied 6 years later. Two of the 126 women classified as hypertensive had died during the 6 years interval since the first examination, both from myocardial infarction. The death rate was similar to the population sample as a whole.


Evidence for peripheral vascular involvement in mild elevation of blood pressure in man. 1. Cardiac output at rest, intra-arterial blood pressure and hand blood flow at maximal vasodilatation were studied in two groups of 18-25 year-old men: forty-four with mild blood pressure elevation were referred from a military enlistment centre, and twenty-nine normotensive volunteers were mainly recruited from the same enlistment centre. 2. The study group was characterized by a significantly higher cardiac index at rest, and a significantly higher blood flow resistance in the hand at maximal vasodilatation than the control group, indicating the presence of structural modifications in the resistance vessels of patients with mild blood pressure elevation. 3. The tendency to increased vascular resistance in the blood vessels of the hand at maximal vasodilatation was more pronounced in patients with a normal cardiac index than in those with a high index. This suggests inclusion in the study group of tense, anxious individuals with an elevated cardiac index but otherwise normal circulation, but does not exclude the possibility that these patients may develop structural changes later on.


Effectiveness of screening for hypertension in Scotland. 1. Data from long-term follow-up of subjects screened for hypertension indicate that the elevation of blood pressure represents a major contribution to community-attributable risk of death. 2. Attendance rates at screening, and drop-out rates from follow-up, have been assessed in studies in Glasgow. 3. Screening and follow-up are probably best conducted from general practice, and should be regarded as an extension of good primary care.


Report on progress in the Australian National Blood Pressure Study (NBPS). 1. The National Blood Pressure Study (NBPS) is a single blind trial designed to test the efficacy of active drug treatment in reducing complications from mild hypertension (mean diastolic pressure = 95-109 mmHg). 2. Between 1973 and 1975, four centres screened about 104 000 subjects aged 30-69 years, yielding an estimated prevalence of hypertension (greater than or equal to 95 mmHg diastolic) of 16% and of moderate-to-severe hypertension (greater than of equal to 110 mmHg diastolic) of 1-3%. 3. Some 4000 subjects selected for untreated uncomplicated mild hypertension were randomized to either active treatment (cholorothiazide +alpha-methyldopa and/or a beta-adrenoreceptor antagonist as required) or to matching placebos. 4. At 1 year mean pressures had fallen significantly below entry pressures in both groups but in the active group the fall was greater by a margin of 14-4+/-1-3 (SEM) mmHg systolic and 7-1+/-0-7 mmHg diastolic. At 1 year 5% of subjects in the placebo group had been placed on active treatment on the ethical grounds that pressure had exceeded the mild hypertension limit. 5. Trial end-points (death, morbidity from stroke, hypertensive heart and renal disease, and ischaemic heart disease) number 106 (nine deaths) thus far, of which ischaemic heart disease accounts for 71% and stroke 19%. 6. The duration of trial may need to be extended beyond the original estimate of 5 years.


Identification and treatment of arterial hypertension in general practice. 1. A screening programme has been set up in a group general practice for identifying and treating moderate high blood pressure in men and women aged 45-54 years, and at the same time the identification and treatment of high blood pressure in patients in reference general practices has been monitored. 2. The special measures resulted in a response rate of 68-8%. In the reference practices, 14-9% of patients attending during the study had their blood pressure reading recorded on the monitoring form. 3. The overall prevalence of diastolic blood pressure (phase 4) greater than or equal to 105 mmHg in the special hypertension programme is 3-8 times that observed in the reference practices.


Effect of weight on prevalence of hypertension, and its interaction with the arm circumference: Belgian Hypertension Committee Epidemiological Study. 1. A first sample of a cross-section of the Belgian population was studied. 2. The presence of hypertension or borderline hypertension was established on the basis of two examinations at 1-3 weeks intervals, during which the blood pressure was measured four times after 10 min rest. 3. The prevalence of both hypertension and borderline hypertension increased with age in the two sexes and, independently of age, with the relative weight. 4. The probable effect of arm circumference in overestimation of blood pressure in heavy subjects was analysed by multivariate correlations. It was concluded that if the influence of arm circumference is excluded, the effect of relative weight on blood pressure is less marked but still present.


Alcohol use, hypertension and coronary heart disease. 1. Male death rates from hypertension and stroke in England and Wales in 1949-53 were highest in those socio-economic and occupational groups with the highest death rates for cirrhosis of the liver (and presumably with highest alcohol intake. 2. In prevalence data from the Busselton population in Western Australia in 1969, there was a significant association between hypertension and a history of heavy drinking. 3. Together with other data, these observations suggest that up to 30% of hypertension in affluent countries may prove to be attributable to the use of alcohol.


A 40 years' follow-up study of 1000 untreated hypertensive patients. 1. This study includes 1038 patients (325 men and 713 women) who consulted the medical out-patient clinic, Rigshospitalet, Copenhagen, during the years 1932-38. All these patients had a blood pressure of 160/100 mmHg or 180 mmHg or more. 2. The average age at the first examination was 54 years; 97% were followed at intervals of 10 years until 1975, when sixty patients were still alive. Treatment was minimal until 1970. 3. Sixty percent of the men and 76% of the women reached an age of 65 years or more. Nine percent of the total patients lived to 85 years or more. Excess mortality was far higher in men than in women. 4. Causes of death were stroke in 17%, heart failure in 24%, coronary occlusion in 16%, uraemia in 4% and other diseases in 39%. At the first examination, thirteen cases of malignant hypertension were registered, none at later sessions.


Blood pressure and its spontaneous variations in a northern Italian population. 1. Blood pressure has been measured in a random sample of 5852 subjects (both sexes, 20-64 years old). The prevalence of hypertension (blood pressure greater than or equal to 160 mmHg and/or 95 mmHg; 150 mmHg and/or 90 mmHg under the age of 30 years) was 29-5%. 2. In a cohort of 972 detected hypertensive subjects, longitudinal changes (2 and 5 months after the initial examination) were evaluated. The phenomenon of regression toward the mean value was evident. 3. The implications of the variability of blood pressure in a community control programme of hypertension are discussed.


Blood pressure response to physical activity in hypertensive subjects at different times of the day. 1. Active orthostasis causes a fall of systolic blood pressure in the morning; this fall was more extensive in severe arterial hypertension. 2. Everyday physical activity produces a marked rise of systolic blood pressure, which is higher at noon and in the evening than in the morning; the hypertensive response is somewhat greater in WHO II and III, than in WHO I, grades of hypertension. 3. In studies on blood pressure behaviour in hypertensive subjects the circadian variability not only of the blood pressure at rest but also of the blood pressure response to various stimuli has to be considered.


Blood pressure and heart rate response to isometric exercise and mental arithmetic in normotensive and hypertensive subjects. 1. Sustained hand-grip exercise and mental arithmetic were performed by normal and hypertensive subjects. Blood pressure and heart rate were recorded with a device which allows blind and unbiased measurements, based on the conventional cuff method. 2. Both stimuli caused increases in heart rate and systolic and diastolic blood pressure, which were greater for isometric exercise than for mental arithmetic. 3. Normal females had a greater response to repeated exercise, and had a smaller systolic pressure elevation during mental arithmetic than the other groups. 4. Repeated testing showed good reproducibility in normal subjects.


Reversed diurnal blood pressure rhythm in hypertensive pregnancies. 1. Reversal of the normal diurnal blood pressure pattern has been demonstrated in women with severe hypertension and renal impairment in pregnancy (pre-eclampsia). 2. Maximum arterial pressure occurred at night in these women. The phenomenon was not due to hypotensive drug therapy or posture. Patients with uncomplicated essential hypertension in pregnancy retained a normal diurnal blood pressure pattern. 3. Nocturnal hypertension in pre-eclampsia is of theoretical interest and practical importance.


Accelerated hypertension in the rat: relation between renin, renal vascular lesions, salt intake and blood pressure. 1. Complete ligation of the aorta between the origins of the two renal arteries in the rat produces a predictable form of accelerated hypertension. Changes in the blood pressure, plasma renin activity and renal histological lesions have been studied. 2. Group 1 rats and their control group (group 2) received tap water, and group 3 and its control group (group 4) received sodium chloride solution (0-154 mol/l) in place of tap water, for 4 weeks before aortic ligation. In the experimental groups 1 and 3, complete ligation was carried out. In groups 2 and 4 the aorta and renal arteries were exposed, but not ligated. Interlobular artery lesions were studied on a blind basis and graded 0-4 according to severity. 3. Groups 1 and 3 developed severe hypertension. In group 1 the raised mean arterial pressure showed a significant correlation with increased plasma renin activity. Both mean arterial pressure and plasma renin activity also showed a significant correlation with changes in interlobular arteries. In group 3 the raised mean arterial blood pressure did not show a significant correlation with the depressed plasma renin activity, or with changes in interlobular arteries. A significant correlation was, however, found between plasma renin activity and interlobular artery lesions in group 3. 4. These results suggest that the renin-angiotensin system may influence renal vascular lesions through some mechanism independent of the blood pressure.


Increased renal excretion of arginine-vasopressin during mild hydropenia in young men with mild essential benign hypertension. 1. The rate of renal excretion of arginine-vasopressin was determined during unrestricted fluid intake for 24 h and in response to fluid deprivation for 18 h in nine young men with very mild essential hypertension and compared with that in sixteen normotensive men of similar age. 2. Despite an equivalent osmolar stimulus, excretion of arginine-vasopressin was significantly greater in the reference group than in the reference group. This difference increased progressively with increasing dehydration. 3. We suggest that these findings are mainly due to an increased rate of secretion of arginine-vasopressin in response to mild hydropenia in hypertensive patients and that a moderate increase of release of arginine-vasopressin during periods of fluid deprivation may exert vascular effects and thus influence the perpetuation of hypertension.


Deoxyribonucleic acid repair synthesis: a new factor for defining high blood pressure. 1. The level of DNA repair synthesis has been compared in males diagnosed as having hypertension (diastolic blood pressure greater than or equal to 100 mmHg), males with slightly elevated blood pressure (greater than 95th percentile corrected for age) and males with normal or subnormal blood pressure (less than or equal to 30th percentile corrected for age). 2. The hypertensive males and the males with elevated blood pressure could not be distinguished from each other with respect to the levels of chemically induced repair synthesis, but both were significantly increased over the induced repair synthesis values of individuals with normal or low blood pressure. Since it has been shown previously that lymphocytes with high repair synthesis values also have increased levels of both carcinogen-DNA binding and chromosomal aberrations (Nordén, Scherstén, Thulin, Pero, Bryngelsson & Mitelman, 1975), the biological significance of this variable appears to be of value in discriminating between normal and high blood pressure groups.


The pathogenesis of hypertensive vascular changes in the rat: microscopic and ultrastructural correlation in vivo. 1. This study describes the changes observed in the rat microcirculation in vivo in the transparent tissue chamber of the rat back, during the florid hypertension produced by ligation of the rat aorta between both renal arteries. 2. Besides providing a new model for analysis of the action of therapeutic agents in hypertension, direct evidence of the variation in blood flow in hypertension is discussed. Fixation of the chamber tissues allows direct ultrastructural correlation with the altered function of particular vessels observed and recorded cinemicroscopically in vivo.


Thrombolysis by ultrasound.

Thrombolysis by ultrasound. 1. A new method of destroying thrombi in blood vessels by ultrasound and simultaneously removing them is reported. 2. Experiments were performed in twenty dogs with artificial thrombi in the iliac and femoral arteries and veins. The length of the thrombi ranged from 4 to 5 cm and the age from 12 h to 10 days. The unit used consisted of a generator, a frequency counter, an ultrasonic transducer with the hollow waveguide and a vacuum pump. For protection of the vessel wall the guide is surrounded by a plastic tube. The ultrasonic frequency is 26-5 kHz, the amplitude 25-30 micronm. The time needed to destroy the thrombus by ultrasound and suck out the thrombotic material ranged from 2-5 to 5 min. 3. To check side effects, experiments were performed in forty-four dogs. No significant changes were seen in the fibrinolytic system or microscopic structure of the vessel wall after ultrasound.


Effects of blood pressure reduction on the structural vascular abnormality in skin and muscle vascular beds in human essential hypertension. 1. Vascular resistance at maximal vasodilatation was examined in two vascular beds in two groups of hypertensive patients and in normotensive control subjects before and during anti-hypertensive therapy in the hypertension groups. 2. In one group of twelve untreated patients with essential hypertension, examined with plethysmography and intra-arterial blood pressure recording, a significantly higher vascular resistance at maximal vasodilatation was found in the hands compared with normotensive control subjects matched for age, sex, weight and height. This indicated a structural vascular abnormality in the patient group. 3. After 5 years of anti-hypertensive therapy in the patient group the difference in vascular resistance between patients and control subjects had decreased significantly, indicating a reversibility of the structural vascular abnormality. 4. Vascular resistance at maximal vasodilatation was examined in the calves of twelve untreated patients with essential hypertension and fourteen normotensive control subjects. Plethysmographic technique and indirect blood pressure recordings were used. A significantly higher vascular resistance was found in patients than in control subjects, indicating a structural vascular abnormality also in this vascular bed. 5. Anti-hypertensive treatment for 6 months in the patient group did not change vascular resistance at maximal dilatation, indicating that the structural vascular abnormality remained. 6. During acute reduction of blood pressure in hypertension by means of trimethaphan infusion, blood pressure and blood flow to the hands were reduced proportionally with no change of vascular resistance at maximal vasodilatation. 7. This indicates that resistance at maximal dilatation was unaffected by the acute reduction of blood pressure, in contrast to the findings after prolonged reduction of blood pressure in this vascular bed.


The intrarenal release of renin in the rat. 1. A technique was developed to measure renin concentration in nanolitre volumes of blood. 2. The renin concentration in renal venous blood was higher that in renal arterial blood. 3. The renin concentration in blood from the efferent arteriole was less than in blood from the renal artery and renal vein. 4. Renin enters the circulation distal to the efferent arteriole. 5. The release of renin into the interstitium would allow local formation of angiotensin and the system could act as an intrarenal control mechanism.


Role of the renal nerves in renin release during suprarenal aortic stenosis in cats. 1. Renin release from an intact, innervated kidney and from the contralateral denervated kidney was measured before and during a period of suprarenal aortic stenosis. 2. Aortic stenosis of 10 min duration reduced renal perfusion pressure to 50 mmHg and increased renin release from both kidneys, but the response from the innervated kidney was greater. 3. A study of the time-course of the response during 30 min of aortic stenosis showed that the difference in rate of renin release between the innervated and the denervated kidney is greatest during the first few minutes of aortic stenosis.


Renin inhibitory effect of synthetic phosphorylethanolamine (PE-104) in the rat. 1. The renin inhibitory effect of 2-[4-(4'-chlorophenoxy)phenoxy - acetylamino]ethylphosphoryl-ethanolamine (PE-104) was examined both in vitro and in vivo. 2. PE-104 inhibited the rate of angiotensin formation from dog renin and renin substrate reaction. The Ki value was 2 mmol/l and the inhibition was competitive. 3. In normotensive rats, infusion of PE-104 abolished the increases of blood pressure and plasma angiotensin I concentration due to renin injection. In renal hypertensive rats, infusion of PE-104 decreased blood pressure and this was associated with a decrease of plasma angiotensin I concentration. 4. These observations confirm that PE-104 is a renin inhibitor.


Experiential education for dental hygiene students.


Renin release from isolated rat glomeruli. 1. By the use of a mechanical graded sieving technique a high yield of isolated glomeruli has been obtained from rat kidny. 2. Microscopy and renin assay have shown the presence of renin-containing juxtaglomerular cells attached to these glomeruli. 3. The viability of isolated glomeruli has been confirmed by the ability of the cells to survive and divide in tissue culture and by their exclusion of vital dyes. 4. In superfusion after washout of extracellular renin, the glomeruli actively release constant amounts of renin over 3 h in direct proportion to the number of superfused. 5. Decreasing sodium concentration from 140 to 110 mol/l with constant osmolarity of 305 mosmol/l stimulated renin release by a direct effect on juxtaglomerular cells. 6. Catecholamines stimulated renin release in vitro in proportion to the potency of their action on beta-adrenoreceptors. 7. The system of superfusion of isolated glomeruli provides a technique for studying the influence of mediators leading to renin release acting directly on juxtaglomerular cells, independent of pressure change, tubular sodium, the sympathetic nervous system and circulating hormones.


Communication and curricular change.

Communication and curricular change.


Genesis.

Genesis.


Focus on ethics.

Focus on ethics.


Japanese Association for Dental Science (Nihon Shikaigaku Kai).


List of dental schools.

List of dental schools.


Student clinicians: American Dental Association.


Extending the use of composites.

Extending the use of composites.


Some examples of fluidics applications in the medical field.


Practical aspiration for local anaesthesia.


Nitroblue tetrazolium test in children with acute lymphoblastic leukaemia and malignant lymphomas.


L-asparaginase therapy and its complications in acute lymphoid leukaemia and generalized lymphosarcoma.


The problem of impacted and unerupted teeth.


Evaluation of the hypothalamic-pituitary-adrenocortical axis in chronic leukaemia.


Localization of alkaline phosphatase in subcellular structures of human osteogenic sarcomas. Electron microscopic study of osteogenic sarcomas has revealed association of the product of the reaction for alkaline phosphatase with membranous structures. The structural and function polymorphism of osteogenic sarcoma cells is also shown.


The salivary glands.

The salivary glands.


A technique for developing established cell lines from human osteosarcomas. A method is described which has been successfully used to develop two human osteogenic sarcomas into established lines in culture. This method provides a means whereby cells growing from explanted tumor tissue can be immediately cloned and the fibroblastic (nonneoplastic) cells thus selected against. Both lines have been passaged for over 100 population doublings since cloning and have retained the ability to form colonies from single cells plated at low density without the use of feeder layers or conditioned medium. In culture, the osteogenic sarcoma cells are nonfibroblastic, pile up, and appear to retain a morphological similarity to the in vivo tumors from which they were derived. A karyotype of cells derived from one of the tumors containing a marker chromosome is also presented.


Water fluoridation--an illegal procedure?


Priapism in child with chronic granulocytic leukemia.


The dental status of 572 institutionalized mentally retarded in Israel.


Caries and the planning of dental treatment for five-year-old children. A survey was conducted to assess the prevalence of dental caries in the primary teeth and first permanent molars of five-year-old children and the occurrence of spaces between their primary molars. The representative sample investigated consisted of 965 children attending compulsory kindergarten in Jerusalem. 84% of the children were found to have carious teeth. Average d.i.f. was 4.7 (+/-3.6). The rate of decay was found to be the same in males and females. 30% were found to have eight or more carious teeth and a large number of extractions had to be carried out in this group. Most of the children examined did not have spaces between their primary molars, a fact that necessitated the use of diagnostic radiographs for all cases of extensive treatment. 77% of the children still had no permanent molars. Of those whose permanent molars had erupted, 73% had no caries. A definite association was found to exist between the prevalence of caries in primary teeth and its prevalence in permanent molars. On the basis of the findings it is concluded that compulsory kindergarten is a suitable frame-work for the commencement of organised dental services. Most of the services required may be provided by general dental practitioners who have received some additional specialised training to equip them to treat children. For problematical children--with particular medical or behavioural problems--more specialised treatment can be provided through medical centres in which paedodontic specialists and more sophisticated equipment are available. Currently available manpower in the dental profession is apparently not sufficient and considerable thought will have to be devoted to solution of this problem.


Financial protection.

Financial protection.


Leucocyte and plasma lipids in chronic granulocytic leukaemia.


The transition from post-graduate studies to a new dental school in the University of Tel Aviv.


The effectiveness of a dental education program on oral cleanliness for school children of 11 to 14 years old. A dental health eduction program on oral cleanliness was given to 175 Jerusalem school-children aged 11 to 14 years. The children were divided into three groups, each numbering approximately 60: Experimental Group 1, Experimental Group 2 and Control Group. The study was conducted over an 8-week period. During the first week the Patient Hygiene Performance (PHP)--an oral hygiene index--was recorded for all the children and used as the base line for the study. It was then recorded one month after the education program was transmitted and again two months afterwards. The objectives of the study were: 1) To examine the effectiveness of a program for providing dental health information and teaching oral hygiene practice to elementary schoolchildren. 2) To find the best method of instruction in the use of toothbrushing. 3) To measure the effectiveness of toothbrushing instruction by testing toothbrushing performance over a given period. The dental health education program consisted of a lecture, 40 animated color slides and toothbrushing instruction given individually and to a group. The results indicated that the education program presented together with toothbrushing instruction improved oral cleanliness and toothbrushing skill. The group receiving individual toothbrushing instruction showed the greates improvement in home care oral cleanliness and in standard of toothbrushing performance skill. Oral cleanliness and toothbrushing skill (taught by both methods) improved with time. Girls showed a slight but constantly greater level of improvement in both oral cleanliness and tooth brushing skill.


The introduction of dental health insurance in Israel.


The Royal Colleges and the NHS.

The Royal Colleges and the NHS.


Malignant bone tumors of the lower extremity. The malignant bone lesions discussed in this paper are those commonly encountered by the podiatrist. An attempt is made to review basic important information concerning these lesions, along with relevant pathologic and histologic characteristics which are necessary for a correct diagnosis. Points of controversy exist regarding classification and histologic and pathologic findings. This makes one realize that a great deal more must be learned about these dreaded cancers so they may be treated more effectively. The podiatrist should be fully able to diagnose these malignant tumors in the foot and lower extremity.


Using case histories in health sciences education--an example: leukemia.


Super 8 films, fundamentals and projection.


Studies on parathion poisoning I. Determination of urinary p-nitrophenol.


Antihypertensive treatment and plasma renin activity in essential hypertension.


Hospital oral dentistry and the patient: some financial aspects.


Biochemical studies on precatorine. (II) Insulinase inhibitory action of L-tryptophan and its N-methyl derivatives.


Studies on the tissue specificity of 125I-alpha-bungarotoxin.


Further studies on mechanism of anticholinesterase activities of cardiotoxin, protamine and polylysine.


Analysis of the four tuberculosis prevalence surveys in Taiwan.


Immune response during hyperimmunization. (XV) Localization of the effect of complete Freund adjuvant on the antibody forming system by means of cytotoxicity test and hemolysin titration.


Horizontal non-parallel pinning for lower anterior teeth.


Changes of drug-resistant patterns of bacteria isolated at National Taiwan University Hospital during 1969-1973.


Pure red cell aplasia treated with immunosuppressive and erythropoietic stimulant agents. Report of two cases.


Terminal aortic obstruction - Leriche syndrome.


Sepsis in the child: review and pathophysiological correlation.


Psychology and dental care.

Psychology and dental care.


Pulmonary resection for metastatic disease: a report of five cases.


Transthoracic placement of sutureless ("screw-in") myocardial electrodes for permanent cardiac pacing.


Third ventricular meningioma: a case report.


Narcolepsy: a case report.

Narcolepsy: a case report.


Abortion in South Carolina.

Abortion in South Carolina.


Immunization against swine influenza: a major challenge for South Carolina physicians. Introduction.


The treatment of syphilis.

The treatment of syphilis.


The swine influenza virus: a perspective.


Influenza immunization in South Carolina.


Clinicopathological conference of the Medical University of South Carolina: Hypotension and electrolyte imbalance with calcification in the right adrenal gland.


Osteoid osteoma: a cause of monoarticular joint pain. Three case reports.


Pyrantel pamoate in the treatment of ancylostomiasis.


Pinworm infestation: a statewide study.

Pinworm infestation: a statewide study.


Environmental sanitation -- a needed supplement in a prevention program for the eradication of intestinal parasites in human populations due to fecal-contaminated soils?


The grammar of the tic in Gilles de la Tourette's syndrome.


A contribution to the interrelation of lipid and uric acid metabolism.


Effect of obesity and its treatment on hyperlipoproteinaemia.


Determination of magnesium in bioptic material by the method of atomic absorption.


Respiratory function and effect of exertion in sarcoidosis and chronic interstitial pulmonary fibrosis.


Quantitative bacteriuria in patients under regular dialysis treatment with terminal urine output.


Single-purpose atomic absorption spectrophotometer for the determination of magnesium.


Exposure tests in trinitrotoluene workers.


Incidence of Hodgkin's disease in siblings.


A contribution to the question of uric acid as a risk factor in the development of ischaemic heart disease.


The therapy of obesity and anorectics.

The therapy of obesity and anorectics.


Ultrasonic examination of the liver (B-scan).


Monitoring the patient in acute respiratory failure.


Free sulphydril groups in the serum in acute myocardial infarction.


Industrial compounds in Port Moresby.

Industrial compounds in Port Moresby.


Arsenic poisoning associated with the burning of arsenic-treated timber.


A deadly cure for lice - a case of paraquat poisoning.


Welder's lung.

Welder's lung.


A preliminary survey of soluble lead in household utensils in Port Moresby.


Roentgenologic studies of the temporomandibular joint in patients operated on mandibular protrusion. Long term results.


Noise induced deafness and its prevention.


Lae sheltered workshop.

Lae sheltered workshop.


Occupational health in Papua New Guinea.


The situation of women in Papua New Guinea.


Workers' role in population control programme.


Can pre-employment medical examinations be simplified?


The role of occupational hygiene in the prevention of occupational health hazards.


The Australian disease.

The Australian disease.


Alcohol usage as a possible explanation for socio-economic and occupational differentials in mortality from hypertension and coronary heart disease in England and Wales. Alcohol usage as a possible explanation for socio-economic and occupational differentials in mortality from hypertension and coronary heart disease in England and Wales.


Recent highlights from the Framingham study.


The relative importance of the major risk factors in atherosclerotic and other diseases. Examination of results from the Framingham study shows considerable disparity between the various clinical conditions which are grouped together as atherosclerotic diseases in their relationship to systolic blood pressure, serum cholesterol level and cigarette smoking. The outstanding features are the dominance of blood pressure in cerebral conditions and the apparent unimportance of smoking in angina pectoris. Analysis of results from the National Co-operative Pooling Project shows that up to 70% of cardiac conditions in this category may be related to these three risk factors with each being of approximately equal importance. Further evidence suggesting that these factors are of greater importance than is commonly realised for non-cardiovascular deaths has been derived from results in the Chicago Peoples Gas Company Study. Though not conclusive, it is hoped that this analysis adds perspective to considerations of pathogenesis and prevention.


Community control of hypertension.

Community control of hypertension. The adequacy of treatment of hypertension in a community was monitored at triennial mass health examinations. Hypertensives were not adequately retained on treatment until a disease register was developed and a practice nurse given responsibility for maintaining contact with patients on the register. The advent of newer therapeutic agents and intensification of the interest of both doctor and patient in the results of treatment were associated with progressive improvement in the adequacy of control of blood pressure.


Rationalisation of hospital services for stroke patients. Over a six month period, the Royal Melbourne Hospital admitted 25% of the stroke patients expected from the north-west region of Melbourne. When the private sector and Mount Royal Hospital were included, a total of 57% of expected demand was met by the hospital services of the region. The natural history of stroke in in hospital consisted of an early "active" phase with a high death rate and a high investigation rate. Three weeks after admission this activity had largely subsided and it is suggested that the acute general hospital was no longer providing the most appropriate care. Transfer of patients with stroke three weeks after admission to a lower cost care situation with more appropriate use of staff would enable the Royal Melbourne Hospital to meet the demand for hospitalisation from its region.


Prospects for prevention of atherosclerosis in the young. There appears to be a need to protect our young from an atherogenic way of life. The average male child today has one chance in three of a cardiovascular catastrophe before age 60. Atherosclerosis and the conditions which predispose appear to have their onset in childhood. Correctable precursors of cardiovascular disease have been identified, and their contribution to risk has been estimated not only for adults but for college students as well. An analysis of the combined impact of atherogenic risk factors indicates that they exert greater force early in life than later. Although the optimal time to begin prophylaxis is not established, there is evidence to suggest that measures instituted late in life when lesions are advanced is of only limited value. Prevention of atherosclerosis is best viewed as a family affair since the propensity to disease and contributing factors tend to be shared by family members. It is also difficult to implement effectively preventive measures which include dietary changes, weight control, exercise and restriction of cigarettes for one family member without involving the rest of the family. Optimal levels of the correctable precursors of cardiovascular disease are not established for children. However, the rise in serum lipids, blood pressure, weight and blood sugar observed in transition from childhood to adult life is not inevitable, or desirable. Paediatricians can alter the appalling cardiovascular mortality statistics by not allowing the process or the habits and conditions which promote it to reach an irreversible stage. Cardiovascular disease may well begin in childhood with "medical trivia" such as a tendency to obesity, moderate cholesterol and blood pressure elevations, lack of exercise and the cigarette habit. In some respects a heart attack at age 45 can be regarded as a failure of the paediatrician. Awaiting proof of the efficacy of the indicated prophylactic measures is not acceptable since this will be a long time in coming. We must learn how to correct risk factors effectively in childhood as soon as they appear. We must establish goals based on optimal as distinct from usual levels of risk factors. Paediatricians' resolve about prevention of atherosclerosis in childhood needs to be strengthened and we must develop a sense of urgency about this.


Comparison of plasma lipids at birth and in second year of life. The value of measuring plasma lipids at birth as a guide to hyperlipidaemia in the future has been studied in 230 infants. There was a weak overall correlation between the cholesterol concentration at birth and during the second year of life (r = +0-215, P less than 0-05). There was no such relationship for triglyceride concentration. Not one of seven infants showing hypercholesterolaemia at birth had a raised level at follow-up. By contrast, all seven infants whose cholesterol levels exceeded two standard deviations at follow-up had normal values at birth. This discrepancy may reflect the influence of diet on plasma lipids. The mean plasma cholesterol and triglyceride concentrations during the second year were significantly lower in those infants being fed diets that contained increased amounts of unsaturated fat. The likelihood of hyperlipidaemia being found during the second year of life therefore depended more on the nature of the infant's food than on the presence of hyperlipidaemia at birth. The added influence of genetic components was suggested by the finding of a greater prevalence of early cardiovascular events in the families of infants showing hyperlipidaemia at one to two years of age.


Behavioural epidemiology and coronary heart disease: some sources of error and an alternative conceptual model. While the quantity of evidence relating behaviour and coronary heart disease is great, the quality is variable. It is possible to discern two broad categories of research error, the methodological and the conceptual, to account for this. The former may be corrected by sufficiently careful study design: the latter may require a complete re-examination of hypotheses. An alternative conceptual model is proposed in which three components (a) a surfeit of adversity in the absence of support, (b) consequent arousal and activation of the cardiovascular system, and (c) the coexistence of one or more of a well documented set of organic risk factors, allow the integrated and systematic testing of hypotheses relating behaviour and coronary heart disease. The authors are presently employing this conceptual model in the investigation of a number of such hypotheses.


Consensus opinion and observer accuracy in electrocardiography with reference to coronary arteriographic information. In this study reader performance in resting electrocardiographic (ECG) reading and case summary interpretation was investigated. Eight cardiologists were asked to read independently 105 paired ECG--Case summary sheets on either two or four occasions. The order of ECG--Case summary inspection for each sheet was randomized over trials. The results show low levels of inter- and intra-reader reliability when physicians report on ECG traces. Reference to coronary arteriographic information confirms that the resting ECG has limited utility in the detection of coronary artery disease.


Acute myocardial infarction: one year follow-up of 1138 cases from the Perth Community Coronary Register. The one year mortality of patients from the Perth Acute Myocardial Infarction Register surviving the acute episode (first 28 days) is presented. Of 1138 patients suffering definite or possible acute myocardial infarction in one year, 705 (62%) survived 28 days. There were 89 deaths (11-5%) in the subsequent 11 months. One year mortality was related to age but not sex, previous symptoms of coronary heart disease, but not hypertension or diabetes, to tachycardia and congestive cardiac failure at first examination, but not arrhythmias in the acute episode. These observations highlight the importance of protecting the myocardium in the acute phase of myocardial infarction.


New approaches to the management of the Wolff-Parkinson-White syndrome. Pre-excitation has been defined as "a condition in which all or some portion of the ventricular muscle is activated earlier in relation to atrial events, than would be expected had the impulse reached the ventricle by way of the normal atrioventricular conduction system". The susceptibility of patients with pre-excitation to paroxysmal tachycardias had been described many years previously. The Wolff-Parkinson-White syndrome was initially thought to have a relatively benign prognosis. Subsequently, it was recognised that some patients were prone to life-threatening arrhythmias and sudden death. This recognition has given impetus to sophisticated electrophysiological study of the pre-excitation syndromes by recently developed techniques of catheterisation, epicardial mapping and surgery. The purpose of this review is to highlight the recent advances in management of the Wolff-Parkinson-White syndrome which have been based upon these electrophysiological techniques.


Changing results of treatment of infarction in a coronary case unit. A comparison has been made between the first 300 patients admitted from 1963 to 1967 to the Coronary Care Unit (CCU) of The Royal Melbourne Hospital with transmural cardiac infarction, and two groups of similar numbers admitted in 1969 and 1974. While the age spectrum and duration of stay of survivors in the Unit has remained similar, there has been a reduction in mortality, most marked in the most recent group of patients. The improvement was seen in all age groups, but was statistically significant only in the patients under 50 years and over 70 years. The reduction occurred in both sexes and was most evident in the patients admitted with severe cardiac infarction. The improvement in results of treatment is due in part, at least, to improvements in management introduced since 1963.


Murray Valley encephalitis in Australia, 1974: antibody response in cases and community. Fifty-three patients accepted on clinical grounds as cases of Murray Valley encephalitis (MVE) in Australia in 1974 were examined for antibody to MVE virus. Only one (who died early in the disease and whose diagnosis was confirmed by virus isolation) did not develop antibody; 13 patients showed stationary or single convalescent titres not diagnostic of recent infection, but other evidence that infection was recent was obtained in eight; 39 showed significant rise or fall in titre confirming recent infection. Haemagglutination-inhibition (HI) was more effective in establishing a diagnosis than complement-fixation (CF) although both tests were of value. Patients varied widely in timing and magnitude of rise and fall of titre. Two showed late rises in antibody titre which raises the possibility of recrudescent persisting infection. CF titres were enhanced in some sera by increase in the number of units of antigen used and by inactivation at 56 degrees C rather than 60 degrees C. Five patients with clinically-acceptable diagnoses of MVE (and one with minor illness) showed higher HI titres to Kunjin than to MVE virus. The results in several cases suggest that Kunjin virus was the infecting agent. In others it is possible that MVE infection had occurred in patients with pre-existing Kunjin antibody. HI reactivity to MVE virus was found in IgM fractions of sera taken for at least 40 days and in some cases for over 100 days after onset of symptoms. IgM fractions gave similar titres to MVE and Alfuy virus but clearly distinguished MVE-Alfuy and Kunjin viruses. HI antibody to MVE virus was found in about 10% of sera from family contacts or neighbours of patients with encephalitis, and in a similar proportion of patients in Victoria with various febrile illnesses not accepted as MVE. One patient with minor illness had antibody response to Kunjin virus. 2589 sera from pathology laboratories in towns in the Murray Valley gave additional evidence of community immunity to flaviviruses and suggested some increase in the proportion reactive between January and May 1974. HI and plaque reduction tests on these sera also gave evidence of antibody to Kunjin virus in the Murray Valley.


Plasma heparin concentrations during subcutaneous heparin therapy. Plasma heparin concentrations were measured at two-hourly intervals following the subcutaneous injection of varying the doses of heparin. With doses of 5000 and 10,000 units, peak plasma concentrations were seen most commonly four hours after the injection. There was a wide range of peak values at both dose levels with considerable overlap and no correlation could be shown between plasma heparin concentration and the age, sex or weight of the individual. Traces only of heparin could be detected in the blood after a 1000 unit injection. Comparable results were obtained up to six hours after the injection with either the calcium or sodium salts of heparin.